The Toll-like receptor (TLR) family of proteins is an integral part of the human innate immune system (Medzhitov et al., 2000, Cytokine Growth Factor Rev., 11:219-232; Akira et al., 2001, Nat. Immunol., 2:675-680). The function of the innate immune system is thought to be the recognition of invading pathogens, the activation of inflammation to control pathogen spread and the subsequent activation of an adaptive immune response specifically directed to the elimination of the pathogen.
TLR2 recognizes a variety of microbial molecules (Lien, 1999, J. Biol. Chem., 274:33419-33425; Yoshimura et al., 1999, J. Immunol., 163:1-5; Underhill et al., 1999, Nature, 401:811-815; Brightbill et al., 1999, Science, 285:732-736; Aliprantis et al., 1999, Science, 285:736-739; Means et al., 1999, J. Immunol., 163:6748-6755). For example, the TLR2 receptor participates in the recognition of Gram positive bacteria, peptidoglycan, lipopeptides, and zymosan from yeast cell walls. Also, Leptospiral LPS (lipopolysaccharide) exerts its activity in a TLR2-dependent manner (Werts et al., 2001, Nat. Immunol. 2:346-352). TLR2 is involved in recognition of viable M. tuberculosis as well as recognition of lipoarabinomannan from rapidly growing mycobacteria (Means et al., 1999, J. Immunol., 163:6748-6755; Means, et al., 1999, J. Immunol., 163:3920-3927). Numerous additional ligands are recognized via TLR2 (reviewed in Lien et al., 2002, Crit. Care Med., 30:S1-11). In studies of TLR1 and TLR2 knockout mice, the receptors were shown to cooperate in recognition of B. burgdorferi outer surface protein A lipoprotein OspA (Alexopoulou et al., 2002, Nat. Med., 8:878-884). Knockout studies have also suggested that TLR1 and TLR2 cooperate in the recognition of 19 kDa mycobacterial lipopeptide and several synthetic triacylated lipopeptides (Takeuchi et al., 2002, J. Immunol., 169:10-14).